Adrenomedullary Response to Hypoglycemia in First-degree Relatives of Patients with Rheumatoid Arthritis

Our recent studies showed blunted adrenomedullary responses to insulin‐induced hypoglycemia in premenopausal females with rheumatoid arthritis (RA) and systemic sclerosis, suggesting dysregulation of the adrenomedullary hormonal system (AMHS). Since no relationship has been found between degree of AMHS dysfunction and clinical or inflammatory parameters in those patients, we hypothesize the presence of an inherited perturbation of the AMHS. To test this hypothesis, we evaluated adrenomedullary responses to insulin‐induced hypoglycemia (0.1 IU/kg) in premenopausal female subjects: 17 glucocorticoid‐naïve RA patients, 15 healthy first‐degree family members (FDR), and 18 age‐ and body mass index–matched healthy controls. Our results demonstrate that when compared to controls, RA patients had lower baseline epinephrine levels (P= 0.01) and lower area under response curve (AUC) levels of norepinephrine (P < 0.001) and epinephrine (P < 0.003). In contrast, FDR had lower (P= 0.001) AUC levels of norepinephrine compared to controls and higher (P= 0.033) AUC levels of epinephrine compared to RA patients. There were no significant differences in epinephrine response between FDR and controls. Although we found lower norepinephrine responses to hypoglycemia in FDR of RA patients, adrenomedullary responses to hypoglycemia does not appear to be altered to the degree found in RA patients.